Alzheimer's disease (AD) causes a progressive, devastating dementia that will affect over 6 million Americans this year. There is an urgent need to develop new therapies. A key element of the NIH AD Research Summit 2012 recommendations was to reexamine our approach to therapies to take into account emerging omics data and exploit network and systems based approaches (e.g. quantitative and systems pharmacology (QSP)) as an adjunct to traditional one-gene, one-receptor, one-mechanism based methods. We propose a planning group to design and begin to implement an approach to therapeutics that focuses on understanding patient heterogeneity (right patient), differences in disease pathophysiology at each stage of the disease (right time) and novel validated drug targets with cognate pharmacological probes by collecting and modeling systems levels perturbations in model systems (right drug). The planning group is designed to leverage emerging -omics data from various time points in the disease process in order to discriminate systems wide changes that occur as a consequence of genetic risk, of early degenerative changes, associated with classical neuropathological and neuroinflammatory changes, and ultimately due to neural system collapse. Both Alzheimer and non-Alzheimer domain expertise has been and will be recruited to design a pipeline based on profiling platforms first in model systems and then in humans to create actionable biomarkers for different endophenotypes, target engagement, and surrogate endpoints for clinical trials. In addition, the planning effort wil examine issues highlighted by RFA 14-017 as potential barriers to the rapid and effective development of therapeutics: we will broadly consider clinical trials input at each stage of the planning and strategic funneling of proposed targets; we will critically examine the institutional infrastructure required to break down non- scientific barriers to successful sharing of information and program expertise; we will organize and carry out workshops, seminars, and a series of face to face meetings to enhance collaborations and knowledge base of Alzheimer and non-Alzheimer domain experts in relevant overlapping topics of interest, with special emphasis on the iterative processes enabled by QSP approaches. This effort will include opportunities for mini- sabbatical exchanges of AD research scientists in QSP focused laboratories. An informatics superstructure will be designed to both enhance collating of data streams form a variety of -omics programs and also enhance communication and collaboration among the work groups envisioned. In additional to a fully-developed plan for a translational Center for Alzheimer's Therapeutic Science, concrete deliverables from the planning process include: (i) evaluation of informatics platforms for storage and distribution of AD data (ii) an opinion or review paper on the application of root cause (failure) analysis to clinical trials for AD and (iii a dozen or so webinars on the application of QSP approaches to AD from leading investigators across multiple disciplines.